Cysteine is a sulfur containing amino acid, which includes three forms--the optically active D-form, the optically active L-form and the optically inactive DL-form (racemate) which is an equivalent weight mixture of the D-form and the L-form. At present, L-cysteine is a predominant product, because it is industrially produced by extraction from hydrolyzates of natural materials (for example, hair and wool, etc.), and it has been used for producing medicines, food additives, cosmetics and feed stuffs, etc. However, there is a problem in that the supply of the raw material is unstable because it is obtained from natural materials. Thus, various processes for synthesizing it by chemical means using chemicals readily available as raw materials have been studied. However, when known processes are utilized, optical resolution must be carried out in order to obtain only the L-form, because the form of cysteine synthesized by chemical means is the DL-form. On the other hand, recently, D-cysteine has been discovered to have a medical effect, but this form is difficult to find in natural materials. Thus, no suitable process is known for obtaining this form, except a process which comprises racemizing the L-form obtained from natural materials such as those described above to form the DL-form or synthesizing the DL-form by chemical means, and carrying out an optical resolution.
Generally various processes such as a physicochemical process, a chemical process, a biological process or an enzymatic process, etc., are known for the optical resolution of racemic organic compounds. Many approaches, including those for glutamic acid, have been developed in case of amino acids. In the optical resolution processes used hitherto, the most industrially advantageous process is believed to be the so-called inoculation crystallization process which is capable of preferentially crystallizing the L-form or the D-form from an aqueous solution of the racemate. However, resolution of many amino acids cannot be carried out by the inoculation crystallization process, because the DL-form thereof forms a molecular compound. Therefore, the production of crystal forms from which resolution can be carried out has been sought, for example, by conversion into salts of organic or inorganic acids, metal salts, N-acylated derivatives and so on of the amino acids. However, the ability to predict the formation of crystals from which resolution can be carried out for individual amino acids has not been developed yet. Accordingly, under present conditions, crystal forms from which resolution can be carried out are basically determined empirically as a result of many experiments.
With respect to cysteine, some reports exist on chemical processes, for example, a process which comprises converting cysteine into an N-acyl-S-benzyl derivative, adding thereto an optically active agent for resolution and carrying out the resolution by utilizing the difference in solubilities of the formed diastereomers. However, a process for physicochemically carrying out the optical resolution of cysteine directly is not known. Namely, not only does cysteine have a comparatively low solubility in a neutral aqueous solution but it is easily oxidized by dissolved oxygen to form cystine. Particularly, oxidation of cysteine is remarkably accelerated when a very small amount of metal ions such as iron or copper is present. Further, because DL-cysteine forms a molecular compound and has a slightly lower solubility in water than the L-form (or the D-form) [in attached FIGURE, curves .circle.4 and .circle.3 show the solubility in water of DL-cysteine (racemate) and the L-form or D-form of cysteine, respectively], it is impossible for resolution to be carried out by inoculation.